Delayed puberty is defined as a lack of physical manifestations of sexual maturation in girls at a chronological age that is two standard deviations above the mean age at the onset of puberty. This can be further subdivided into several classification based on disorders that affect operation of the luteinizing hormone-releasing hormone (LHRH) pulse generator, the pituitary gland, or the ovary. This includes idiopathic (constitutional) delay in growth and puberty, hypogonadotropic hypogonadism, and hypergonadotropic hypogonadism.
Idiopathic delay in growth generally applies to those girls who spontaneously enter puberty after the normal age of twelve. In most cases, the first signs of secondary sexual development occurs within one year after treatment with LHRH or within one year after gonadotropin and estradiol concentrations begin to increase spontaneously. Thus, the child usually reaches her full genetic potential in height and attains full sexual maturity, but it takes longer than usual. Growth velocity in subjects with constitutional delay in growth and adolescence returns to normal after the onset of puberty. Treatment of delayed puberty depends on the the nature and severity of the disorder. Often treatment of delayed puberty for girls consists of a three month course of estrogen replacement to initiate maturation of the secondary sexual characteristics.
Insufficient pulsatile secretion of LHRH and the resulting follicle-stimulating hormone (FSH) and LH deficiency also leads to sexual infantilism. The LHRH deficiency may be secondary to a genetic or developmental defect, or may be due to a tumor, inflammatory response, vascular lesion, or trauma. There are a variety of causes and disorders associated with the disease. Gonadotropin deficiency may require treatment with estrogen replacement therapy at an age approximating the normal age of puberty onset and continued until fertility is reached.
Primary ovarian failure and the impaired secretion of estrogen leads to a decreased negative feedback and elevated LH and FSH levels termed hypergonadotropic hypogonadism. This commonly is exhibited as Turner's Syndrome and is treated with hormone replacement of estradiol beginning at age tweleve or thirteen to allow secondary sexual development at the appropriate chronological age.
Ovarian dysgenesis can be caused by many factors. Failure of ovarian development or ovarian dysgenesis is commonly associated with hypopituitarism in childhood. Deficiency of the thyroid and adrenal cortex is currently corrected with replacement therapy, and the failure of sexual development is treated with estrogen.
Treatment at the normal age of puberty with hormone replacement can be expected to have drawbacks. In addition, estrogens at high doses accelerate epiphyseal bone closure in tall girls, but is rarely used because of the side-effects associated with such high dose regimens. Therefore there exists a need to find new methods for treating and/or preventing the above.